反应详情

温度

100 °C

A reaction flask was charged with copper iodide (50.4 mg, 0.265 mmol), sarcosine (N-methyl glycine) (37.7 mg, 0.42 mmol), benzenesulfonamide (251 mg, 1.59 mmol), (4aR,7aS)-1-(4-fluoro-benzyl)-4-hydroxy-3-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-1,4a,5,6,7,7a-hexahydro-[1]pyrindin-2-one (prepared as described in Example 39c, 300 mg, 0.53 mmol) and potassium phosphate (338 mg, 1.59 mmol). The flask was degassed and backfilled with nitrogen, and then anhydrous N,N-dimethylformamide (8 mL) was added. The resulting suspension was vigorously stirred at 100° C. for 16 h, and then allowed to cool to 25° C. The mixture was passed through a plug of Celite and washed with 10% methanol/dichloromethane. The filtrate was concentrated in vacuo, and the residue was purified by prep-HPLC [Column Luna 5μ C18 (2) 100 Å AXIA 50×21.2 mm, 5 micron, 40%-95% in 7 min @ 30 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water] to afford the desired product, (4aR,7aS)-N-[3-[1-(4-fluoro-benzyl)-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-[1]pyrindin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-benzenesulfonamide (110 mg, 0.19 mmol, 35%), as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.40-1.60 (2H, m), 1.94 (1H, m), 2.05 (1H, m), 3.29 (1H, bs), 3.84 (1H, bs), 4.46 (1H, bs), 4.86 (1H, d, J=14.4 Hz), 7.14 (2H, t, J=9.6 Hz), 7.35-7.43 (4H, m), 7.47-7.62 (4H, m), 7.74 (2H, m), 10.75 (1H, s). LC-MS (ESI) calcd for C28H25FN4O6S2 596.12, found 597.2 [M+H+].

1. customThe flask was degassed
2. additionanhydrous N,N-dimethylformamide (8 mL) was added
3. temperatureto cool to 25° C
4. washwashed with 10% methanol/dichloromethane
5. concentrationThe filtrate was concentrated in vacuo
6. customthe residue was purified by prep-HPLC [Column Luna 5μ C18 (2) 100 Å AXIA 50×21.2 mm, 5 micron, 40%-95% in 7 min